1. Field of the Invention
This invention relates to new vitamin E intermediates and methods for their preparation.
2. Prior Art
During the past years, vitamin E (.alpha.-tocopherol) has gained importance as antioxidant as well as in the field of human and animal nutrition. The most diverse methods are known for synthesizing all-rac-.alpha.-tocopherol. A survey by Siebrell and Harris on this subject is found in Vitamins, vol. V, pages 165 seq, (1972). The more recent literature also contains methods for the preparation of natural, optically active vitamin E (2R,4'R,8'R-.alpha.-tocopherol) (compare also N. Cohen et al, Journal of the Americal Chemical Society, 101 (1979), pages 6710-16). The preparation of stereoisomers of .alpha.-tocopherol is of interest since the various stereoisomers have a varying biological effect. Among the three asymmetry centers of the natural vitamin E having formula ##STR4## the center at the carbon atom in the 2-position is of particular importance for the biological effect (compare S. Ames, Lipids No. 6 (1971), pages 281-290, particularly page 285). Thus, for example, the (2R,4'RS,8'RS), compared with the (2S,4'RS,8'RS) epimer is five times more effective. Because of the multi-stage and complicated nature of the known processes, the synthesis of RRR-.alpha.-tocopherol appears cumbersome and technically hardly implementable. However, since centers C-4' and C-8' influence the effectiveness of the molecule on a subordinate scale only, a synthesis of (2R,4'RS,8'RS)-.alpha.-tocopherol is already sufficient to achieve increased biological activity.
In Helv. Chim. Acta, vol. 64; Fasc. 4 (1981), pages 1158-73, Cohen et al describe the preparation of all eight possible stereoisomers of .alpha.-tocopheryl acetate in high chemical and stereoisomeric purity. The (2R,4'RS,8'RS)isomer was obtained, for example, by reacting racemic tetrahydronerolidol with triphenylphosphonium bromide in CH.sub.2 Cl.sub.2 and Wittig reaction of the resultant triphenylphosphonium salt with (+)-(S)-6-benzyloxy-2,5,7-tetramethylchroman-2-carbaldehyde in the presence of sodium methylate and subsequent hydrogenation of the resultan .alpha.-tocopherol on Pd/Charcoal.